This invention relates to a method for producing a test cell for use in a magnetic immunoreaction diagnostic apparatus using a magnetic marker. More specifically, the invention relates to the provision of a test cell for magnetic immunoreaction assay, which comprises a polymer having a quantity of residual magnetism, as measured by a SQUID sensor, of 15 pT or less, and also relates to a method for forming a test cell for magnetic immunoreaction assay from such a material.
In the field of so-called biomeasurement, such as detection of pathological microorganisms and cancer cells, DNA gene analysis, or detection of environmentally hazardous substances, it is common practice to measure the binding of a biological substance (antigen), which is to be measured using an immunoreaction, to a test reagent (antibody), which selectively binds to the biological substance, thereby measuring the type and amount of the antigen.
The detection of a biological substance has hitherto been performed by an optical technique which detects the biological substance with the use of an optical signal from an optically labeled antibody. In this optical technique, an optical marker such as a luminescent enzyme is addition-reacted with a test reagent (antibody), and light from the marker is measured to detect the biological substance. Currently, the lower limit of detection of a biological substance by this optical technique is said to be several picograms. Thus, the optical technique has become unable to fulfill a requirement for high sensitivity to those biological substances which are present in trace amounts of the order of several picograms or less at local sites or in the bloodstream. See, for example, the following patent documents or non-patent documents:                Japanese Patent No. 2532670        Japanese Patent Application Laid-Open No. 2000-304749        Japanese Patent Application Laid-Open No. 1997-184841        Japanese Patent Application Laid-Open No. 1997-243641        Japanese Officially Published Patent Gazette No. 1999-508031        K. Enpuku, “Bioimmunodiagnosis using SQUID”, Journal of Cryogenics, Vol. 38, No. 9, pp. 469-476 (2003)        K. Enpuku. “Antigen-Antibody Reaction Measurement using SQUID”, Journal of Applied Physics, Vol. 70, No. 1, p. 48 (2001)        
As one of methods which satisfy the above requirement, a magnetic immunodiagnostic method using a high sensitivity magnetic sensor has been developed. Particularly, a superconducting quantum interference device, called SQUID, which makes use of a quantum effect (quantization of flux) appearing in a superconducting state, is attracting attention as a high sensitivity magnetic sensor, because it enables an extremely weak magnetic field to be measured.
An immunoreaction assay method by SQUID uses a magnetic marker constructed by addition-reacting an antibody with the surface of a polymer enclosing magnetic fine particles. This method measures by SQUID a feeble magnetic field signal issued from the magnetic marker when the antibody produces an antigen-antibody reaction with an antigen contained in a substance to be measured. Since the immunoreaction assay method by SQUID involves a high sensitivity sensor, this method is expected to provide sensitivity which is 100 times or more the sensitivity of a conventional fluorescent antibody assay method. Since the immunoreaction assay method by SQUID is a magnetic method, moreover, it can not only be expected to show high sensitivity, but it also is highly expected in that it can detect a biological substance even present in a solution. Furthermore, the conventional method of detection requires the step of washing off an unbound antibody after a labeled antibody is reacted with a biological substance. In the immunoreaction assay method by SQUID, by contrast, no signal comes from the unbound magnetic marker, and it suffices to detect a magnetic signal from only the marker bound to a biological substance. From the point of view of the washing-off step being omissible, the SQUID-based immunoreaction assay method is considered to be promising.
With the SQUID immunoreaction assay method, an antibody selectively binding to an antigen is used to bind the antigen and the antibody together. At this time, the antibody is addition-polymerized on the surface of a polymeric substance enclosing magnetic fine particles. The antibody with this feature is called a magnetic marker. The reaction between the antigen and the antibody is known from the detection of a magnetic signal from the magnetic marker. In the SQUID immunoreaction assay method, the magnitude of the magnetic signal is proportional to the amount of the magnetic marker bound to the antigen. To detect a weak antigen-antibody binding reaction with high sensitivity and at a high speed, therefore, it is necessary to measure a feeble magnetic signal as an index of detection of a trace reaction.